Bronchial Epithelial IgA Secretion Is Impaired in Asthma. Role of IL-4/IL-13

Ladjemi, Maha Zohra;Gras, Delphine;Dupasquier, Sébastien;Detry, Bruno;Pilette, Charles;et.al.
(2018) American Journal of Respiratory and Critical Care Medicine — Vol. 197, n° 11, p. 1396-1409 (2018)

Files

LadjemietalAJRCCM2018IgAasthma.pdf
  • Restricted Access
  • Adobe PDF
  • 1.33 MB
Request a copy

Details

Authors
Show more
Abstract
(en) RATIONALE: Asthma is associated with increased lung IgE production, but whether the secretory IgA system is affected in this disease remains unknown. OBJECTIVES: We explored mucosal IgA transport in human asthma and its potential regulation by T-helper cell type 2 inflammation. METHODS: Bronchial biopsies from asthma and control subjects were assayed for bronchial epithelial polymeric immunoglobulin receptor (pIgR) expression and correlated to T-helper cell type 2 biomarkers. Bronchial epithelium reconstituted in vitro from these subjects, on culture in air-liquid interface, was assayed for pIgR expression and regulation by IL-4/IL-13. MEASUREMENTS AND MAIN RESULTS: Downregulation of pIgR protein was observed in the bronchial epithelium from patients with asthma (P = 0.0002 vs. control subjects). This epithelial defect was not observed ex vivo in the cultured epithelium from patients with asthma. Exogenous IL-13 and IL-4 could inhibit pIgR expression and IgA transcytosis. Mechanistic experiments showed that autocrine transforming growth factor-β mediates the IL-4/IL-13 effect on the pIgR, with a partial contribution of upregulated transforming growth factor-α/epidermal growth factor receptor. CONCLUSIONS: This study shows impaired bronchial epithelial pIgR expression in asthma, presumably affecting secretory IgA-mediated frontline defense as a result of type 2 immune activation of the transforming growth factor pathway.
Affiliations

Citations

  • APA
  • Chicago
  • FWB

Ladjemi, M. Z., Gras, D., Dupasquier, S., Detry, B., Lecocq, M., Garulli, C., Fregimilicka, C., Bouzin, C., Gohy, S., Chanez, P., & Pilette, C. (2018). Bronchial Epithelial IgA Secretion Is Impaired in Asthma. Role of IL-4/IL-13. American Journal of Respiratory and Critical Care Medicine, 197(11), 1396-1409. https://doi.org/10.1164/rccm.201703-0561oc (Original work published 2018)